Is the retrieval of high numbers of oocytes desirable in patients treated with gonadotrophin-releasing hormone analogues (GnRHa) and gonadotrophins?

Continuous administration of gonadotrophin-releasing hormone analogues (GnRHa) in patients stimulated for the purpose of IVF might have a direct effect on the ovary. We have evaluated the IVF outcome of patients treated with Buserelin and subsequently with a combination of follicle-stimulating hormone (FSH) and human menopausal gonadotrophin (HMG). Patients were divided into three groups according to the number of oocytes obtained by transvaginal ultrasound-guided follicular aspiration: group 1 (n = 35), in which 1-5 oocytes were retrieved; group 2 (n = 30), in whom 6-10 oocytes were obtained; group 3 (n = 32), in whom greater than or equal to 11 oocytes were collected. Only couples with normal semen samples at oocyte retrieval were included in this study. The dose of Buserelin employed was not different between groups. However, the amount of FSH/HMG necessary to reach an optimal response significantly (P less than 0.01) decreased as follicular development increased. The quality of the oocytes obtained was evaluated based on the appearance of the oocyte-corona-cumulus complex, fertilization rate, morphological appearance of the embryos, and implantation rate. The fertilization rate was significantly (P less than 0.01) decreased in group 3 (57.2%) in comparison with groups 1 (77.1%) and 2 (74.2%). There was no significant difference between the groups in the quality of the embryos obtained or the quality of those replaced into the uterus. The implantation rate per embryo transferred was significantly (P less than 0.05) higher in group 1 (16.5%) in comparison with groups 2 (6.6%) and 3 (8.2%).(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of a short regimen of buserelin, a gonadotrophin-releasing hormone agonist, and human menopausal gonadotrophin in assisted conception cycles

The outcome of in-vitro fertilization treatment using buserelin, an agonist of luteinizing hormone releasing hormone, given in a short stimulation regimen with human menopausal gonadotrophin (HMG), was compared with a conventional regimen including clomiphene citrate (CC). A total of 94 infertile women underwent cycles of treatment with intranasal buserelin, 500 micrograms daily from the first day of menstruation and also HMG daily from the third day. The same patients had previously undergone unsuccessful treatment cycles with CC and HMG. Overall, addition of buserelin resulted in fewer cycles being abandoned (10 versus 34%) and none of the patients ovulated prior to collection. The mean total dose of HMG required was increased by 74% in buserelin cycles. Significantly more oocytes were collected with buserelin treatment (mean 5.9 versus 4.4, P less than 0.01) and, thus, significantly more embryos were transferred (mean 2.3 versus 1.2, P less than 0.0001) although fertilization and cleavage rates were unchanged. Fifteen pregnancies were achieved, giving a clinical pregnancy rate of 22% per embryo transfer. These pregnancies resulted in 16 live births (7 singletons, 3 twins, 1 triplets). Four pregnancies failed before 14 weeks gestation. We conclude, therefore, that the substitution of buserelin for CC for ovarian stimulation in poor responders results in an improved outcome, both in terms of the number of oocytes collected and the pregnancy rate per treatment cycle.     

Women with one ovary have decreased response to GnRHa/HMG ovulation protocol in IVF but the same pregnancy rate as women with two ovaries

The study compares the response after gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) stimulation for in-vitro fertilization (IVF) in patients with either one or two ovaries. The study group (group A) included 73 cycles in women who had unilateral oophorectomy before their IVF treatment and the control group (group B) included 988 cycles in women with two ovaries. Tubal disease was the sole cause for infertility in all cases. The two groups were similar in age and parity. The patients with one ovary required more ampoules of HMG (62.9 versus 48.9, P < 0.001), a longer induction period (13.5 versus 12.7, P < 0.01) and had significantly lower oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration (5840 versus 6473 pmol/l, P = 0.035). They yielded fewer follicles (11.2 versus 13.1, P = 0.005), fewer oocytes (7.3 versus 9.1, P = 0.006) and produced fewer embryos (4.4 versus 5.1, P < 0.05). There was no difference in fertilization rate (60 compared with 58%), or pregnancy rate (25.8 compared with 27.1% per oocyte retrieval). Women with only one ovary responded less well to GnRH agonist/HMG stimulation than women who had both ovaries but pregnancy outcome was the same in both groups.      

A randomized comparative study of highly purified follicle stimulating hormone and human menopausal gonadotrophin for ovarian hyperstimulation in an oocyte donation programme

A randomized comparative study of highly purified human follicle-stimulatinghormone (FSH-HP), administered s.c, and human menopausal gonadotrophin(HMG), administered i.m., was carried out in 41 volunteer oocytedonors. The response to ovarian hyperstimulation was similarin both groups. One cycle in both groups was cancelled. Thenumber of oocytes recovered was 16.0 ± 7.9 (mean ±SD) following stimulation with 32.8 ± 103 ampoules ofFSH-HP (n = 19) over 12.3 ± 1.7 days. Following stimulationwith 29.8 ± 10.6 ampoules of HMG over 11.5 ± 1.6days, the number of oocytes collected was 18.4 ± 12.7(n = 20). The oocyte recipients were allocated 9.2 ±3.6 oocytes in the FSH-HP group (n = 33) and 9.6 ± 4.6oocytes in the HMG group (n = 37). The fertilization rate (2PN/cell)was significantly higher in the HMG group (48%, 170/355) thanin the FSH-HP group (36%, 109/304) (P < 0.01). The numberof embryos transferred per recipient was 2.0 ± 0.4 inthe FSH-HP and 2.0 ± 03 in the HMG group. The pregnancyrate per embryo transfer was 25% in the FSH-HP (5/20) and 26%(8/31) in the HMG group. Fertile donors with body mass index£25 made up a poor responder group to s.c FSH-HP, possiblyindicating reduced absorption of the drug.     

In-vitro matured metaphase-I oocytes have a lower fertilization rate but similar embryo quality as mature metaphase-II oocytes after intracytoplasmic sperm injection.

About 4% of all the oocytes denuded prior to intracytoplasmic sperm injection (ICSI) are in metaphase-I (MI). Frequently, these oocytes achieve meiosis after a few hours of in-vitro culture and are available for ICSI on the day of oocyte retrieval. In this retrospective study, the aim was to evaluate the fertilization rate and the developmental capacity of these in-vitro matured MI oocytes. After controlled ovarian stimulation using human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG) in 896 ICSI cycles, 1210 MI-to-MII-matured oocytes were injected approximately 4 h after in-vitro culture and 8803 MII oocytes were injected immediately, or later, after denudation. The fertilization rate of in-vitro matured oocytes was significantly lower than that of mature MII oocytes (52.7 and 70.8% respectively, P < 0.00l). Embryo quality was only slightly different as regards the numbers of good quality embryos: 47.4% good quality embryos were obtained in the in-vitro matured oocyte group, whereas 53.2% good quality embryos were obtained in the MII oocyte group (P < 0.05). The same proportions of excellent (5.7 and 7.0%, NS) and fair quality (17.6 and 15.3%, NS) embryos were obtained for in-vitro matured and mature oocytes respectively. Embryos derived from in-vitro matured oocytes were transferred only if they were of better quality or if there were not enough mature oocyte derived embryos available. Fifteen transfers involved only embryos derived from in-vitro matured oocytes: 11 single embryo transfers and four transfers of two embryos, resulting in one singleton pregnancy and the birth of a healthy baby. It may be concluded that in cycles with few MII oocytes it might be worthwhile to inject in-vitro matured MI oocytes in order to increase the number of embryos available for transfer.     

Outcome of treatment subsequent to the elective cryopreservation of all embryos from women at risk of the ovarian hyperstimulation syndrome.

From 1st June 1989 to 31st May 1991, 78 women with a serum oestradiol level greater than 3500 pg/ml on the day of the ovulatory trigger, following pituitary suppression with buserelin and ovarian stimulation with human menopausal gonadotrophins (HMG), had all their embryos electively cryopreserved at the pronucleate stage to minimize the risk of developing ovarian hyperstimulation syndrome (OHS). Treatment with buserelin was continued in the luteal phase. A median of 19 oocytes (range 7-43) was obtained and 12 embryos (range 1-37) frozen per cycle. Twenty-one (27%) women developed OHS (six severe). Women developing OHS had higher (P less than 0.05) serum oestradiol concentrations on the 7th day after oocyte retrieval, compared to those who did not. No differences were found for any of the following criteria: aetiology of infertility, age, total dose of HMG, number of oocytes, fertilization rate or freeze-thaw survival of embryos. Subsequently, 125 frozen-thawed embryo replacements have been undertaken, using buserelin and hormone replacement therapy (HRT) (n = 93) or natural cycles (n = 32). The overall freeze-thaw survival and implantation rates per embryo were 71.8 and 11.7%, respectively. The pregnancy rates in natural cycles (19%) and buserelin/HRT cycles (29%) were not significantly different.     

Relativity of the concept 'high responder to gonadotrophins'.

Regression analysis of the proportion of unfertilized oocytes on the number of oocytes retrieved per patient was applied to three different ovarian stimulation protocols in order to establish the relativity of the concept 'high responder to gonadotrophins' for in-vitro fertilization (IVF) patients. After fitting the data to the model: probit(proportion of unfertilized oocytes) + 5 = intercept + B Log10(oocytes retrieved per patient), women with a number of oocytes retrieved greater than or equal to the value necessary to obtain 50% fertilization were defined as high responders. Exogenous gonadotrophin stimulation which was commenced after complete suppression of ovarian activity by a gonadotrophin-releasing hormone analogue (GnRHa) (long protocol) resulted in a significantly higher number of oocytes retrieved (10.15) to obtain 50% fertilization compared to a short protocol (6.84) (exogenous stimulation began 2 days after the GnRHa administration). Women stimulated without use of a GnRHa showed an intermediate response. Implantation, pregnancy and miscarriage rates showed no difference between low-moderate and high responders. These results demonstrate the relativity of the concept 'high responder to gonadotrophins' and indicate that the drawback of low fertilization in high responders could be balanced by the high number of oocytes retrieved per patient (and available embryos for transfer) and the selection of the best embryos for transfer.     

Pregnancy rates after transfer of embryos obtained from different stimulation protocols and frozen at either pronucleate or multicellular stages.

After in-vitro fertilization, 2161 supernumerary embryos were frozen with 1,2-propanediol and sucrose as cryoprotectants at either pronucleate or multicellular (2-6 blastomeres) stages. By the end of March 1990, 494 pronucleate stage embryos and 492 multicellular stage embryos had been thawed and 54 and 47% of them, respectively were considered suitable for transfer. Ongoing pregnancy and implantation rates were 17.9 and 10.7%, respectively for embryos frozen at the pronucleate stage and 5.5 and 4.7% for embryos frozen at the multicellular stage. Ovarian stimulation with human menopausal gonadotrophin (HMG) after pharmacological hypophysectomy with a gonadotrophin releasing hormone agonistic analogue (GnRHa) using a long protocol permitted us to freeze significantly more embryos per cycle (7.2 +/- 4.1) than stimulation with HMG and GnRHa in a short protocol (4.7 +/- 3.4) or stimulation with clomiphene citrate (CC) and HMG (2.7 +/- 1.9). Ongoing pregnancy rates after transfer during the stimulated cycles were similar for the three types of treatment (27.1, 27.3 and 32.1%, respectively). However, ongoing pregnancy rates after frozen-thawed embryo transfers were significantly higher when originating from GnRHa + HMG treatments (14.3 and 14.8%, respectively for long and short protocols) than when originating from CC + HMG treatment (5.6%). Embryo cryopreservation has permitted the ongoing pregnancy rate to increase from 28.4 to 36.9% (P less than 0.01) even though more than half of the embryos have not been thawed. We conclude that embryos obtained after stimulation with GnRHa + HMG and frozen at the pronucleate stage are more likely to result in a pregnancy.     

In-vitro fertilization and the ovarian hyperstimulation syndrome.

Eight patients who developed severe ovarian hyperstimulation syndrome (OHSS) were identified among 1302 patients undergoing in-vitro fertilization (IVF) over a 1 year period (prevalence of 0.6%); 63% had ultrasonically diagnosed polycystic ovaries (PCO) and 75% were undergoing their first attempt at IVF. Pretreatment with a superactive luteinizing hormone-releasing hormone (LHRH) analogue significantly increased the prevalence of severe OHSS (1.1% versus 0.2%, P less than 0.05) compared with ovarian stimulation with clomiphene citrate and human menopausal gonadotrophin (HMG). The mean serum oestradiol concentration on the day of human chorionic gonadotrophin (HCG) administration was 8200 +/- 2300 pmol/l. A mean of 19.6 +/- 6.8 follicles had been aspirated and 13.1 +/- 7.7 oocytes recovered at transvaginal ultrasound-directed oocyte recovery. All patients had an embryo transfer and luteal support in the form of HCG. The clinical pregnancy rate was 88%, multiple pregnancy rate 71% and implantation rate 63.5 +/- 41.3%. In a group of seven patients who were hospitalized for moderate OHSS during the same period, peak oestradiol levels were significantly lower than in those with severe OHSS (P less than 0.05). Of the group with moderate OHSS, 57% had PCO, the clinical pregnancy rate was 100% and multiple pregnancy rate 43%. Patients with ultrasound-diagnosed PCO have an increased risk of developing OHSS and the dose of HMG administered to them should be minimized. In patients at risk of developing OHSS, progesterone instead of HCG should be used for luteal support. Transfer of a maximum of two embryos or freezing all embryos for transfer in a subsequent cycle may reduce the likelihood of multiple pregnancy.     

Recombinant follicle stimulating hormone is effective in poor responders to highly purified follicle stimulating hormone

Ovarian stimulation in cases of poor ovarian responsiveness is an important challenge in in-vitro fertilization (IVF) programmes. Despite improvements in oocyte number and quality, an ideal ovarian stimulation strategy has yet to be defined. Here, the results of ovarian stimulation with recombinant follicle stimulating hormone (rFSH) in 28 poor responders to highly purified FSH (FSH-HP) with high basal concentrations of FSH are reported. The protocols used on the FSH-HP and rFSH cycles were identical with the sole exception of the FSH preparation: triptorelin 0.1 mg/day (gonadotrophin-releasing hormone, GnRH-agonist short protocol) and the starting FSH dose of 300 IU/day were administered from day 2 of the menstrual cycle. Ovarian outcome was classified as 'normal', 'intermediate' and 'poor', depending on the number of mature oocytes retrieved and the peak serum oestradiol concentration. Nine of the 28 subjects had an intermediate ovarian response to re-stimulation with rFSH. In the 26 patients who received human chorionic gonadotrophin on both cycles, re-stimulation resulted in a significant increase (P < 0.05) in the mean number of mature oocytes (2.4 +/- 1.4 versus 1.7 +/- 0.8), mean peak oestradiol concentration (606 +/- 252 versus 443 +/- 32 pg/ml) and fertilization rate (73.0 versus 53.3%). Four pregnancies were achieved. It is concluded that rFSH in a GnRH-agonist short protocol improves the ovarian outcome in poor responders to FSH-HP with high basal concentrations of FSH.     

Ovarian stimulation in previous failures from in-vitro fertilization: distinction of two groups of poor responders

Forty-three patients who responded poorly to previous stimulation with clomiphene citrate (CC)/human menopausal gonadotrophin (HMG) for IVF were followed during 70 further cycles. Eighteen patients had a normal FSH response to CC in the previous cycle, while 25 had an abnormal FSH response. Three stimulation protocols were used: buserelin/HMG, CC/HMG and HMG only. No difference between the two groups was observed in the dose of HMG used for any stimulation protocol. More cycles were cancelled due to a poor response in the abnormal response group compared to the normal response group. In the completed cycles, the maximum oestradiol level and number of oocytes retrieved were lower in the abnormal response group compared to the normal response group. The total pregnancy rate per patient, including spontaneous conceptions during the study period, was lower in the abnormal response group compared to the normal response group, 4 versus 33%. We conclude that poor responders with an abnormal FSH response to CC have a latent ovarian failure with a low chance of success in further IVF attempts.     

Comparative auto-controlled study between swim-up and Percoll preparation of fresh semen samples for in-vitro fertilization.

This study compared swim-up and Percoll preparation of fresh semen samples for in-vitro fertilization. Sixty trials of in-vitro fertilization (IVF), 38 with normal semen and 22 with abnormal semen, comprising 734 oocytes were included in the study. Each semen sample was prepared by both a swim-up technique and a simplified discontinuous (50%, 70%, 90%) Percoll gradient. The oocytes for each trial were distributed at random between the two sperm preparations and incubated with the same number of motile spermatozoa. Percoll gradient preparation produced a significantly higher final concentration of spermatozoa than swim-up preparation (mean +/- SEM: 6.6 +/- 1.5 x 10(6)/ml versus 1.9 +/- 0.2 x 10(6)/ml; P less than 0.01) but a significantly lower sperm motility (69 +/- 2% versus 94 +/- 1%; P less than 0.001) and a lower number of normal forms (55 +/- 2% versus 64 +/- 2%; P less than 0.01). The ability of the Percoll gradient method to extract motile spermatozoa was higher than that of the swim-up technique (20 +/- 15.6% versus 0.8 +/- 13.6%). Nevertheless, the rates of fertilization (61%), fertilization failure (18%) and polyspermia (9%), embryo quality evaluated by mean embryo scores (3.8 +/- 0.3) and the mean number of spare embryos frozen per trial (1.4 +/- 0.3) were strictly identical in both groups. The 24 pregnancies (including three from frozen--thawed embryos) obtained in these 60 trials (40% per oocyte retrieval) could not be separated according to the sperm preparation method, as embryos from both groups were replaced together.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transfers of frozen-thawed human embryos in cycles stimulated by HMG

A total of 130 transfers of frozen-thawed (F-T) human embryos was carried out after moderate ovarian stimulation with human menopausal gonadotrophin (HMG). Embryos were replaced 3 days after the spontaneous luteinizing hormone (LH) surge or 4 days if ovulation was induced by human chorionic gonadotrophin (HCG). Embryos were thawed a few hours prior to transfer. One-hundred-and-twenty-three transfers were effective and 23 pregnancies were achieved. The rate of ongoing pregnancies per transfer was 17.9% (22/123). The survival rate of embryos originating from cycles stimulated by a combination of an LHRH analogue and HMG in a long protocol (LA-HMG protocol) was significantly lower when compared with the rate of embryos retrieved from clomiphene citrate-HMG (CC-HMG protocol) stimulated cycles (52 versus 67%, P less than 0.05). When fresh embryos originated from cycles stimulated with an LHRH analogue and HMG in a short protocol (SA-HMG protocol), the survival rate was not affected (59 versus 67%, NS). Although the difference was not significant, the ongoing pregnancy rate per transfer according to the three protocols from which the embryos originated seemed to be better with the SA-HMG protocol: 16% with the CC-HMG protocol, 14.5% with the LA-HMG protocol versus 27.6% with the SA-HMG protocol. The success rate was independent of the number of F-T transferred embryos if at least one embryo with 100% intact blastomeres was replaced.     

Addition of GnRH antagonist in cycles of poor responders undergoing IVF

Concern about the use of gonadotrophin-releasing hormone (GnRH) agonists in ovarian stimulation of poor responder IVF patients has arisen from the claim that GnRH agonists might have a direct deleterious effect through their receptors on the ovary. In this study, we compared two ovarian stimulation protocols in which no GnRH agonists were used. In all, 40 patients with a poor response in previous treatment cycles were included. They were divided into two groups: group I (n = 20) received ovarian stimulation for 20 cycles, without the addition of either GnRH agonist or antagonist; while group II (n = 20) patients received ovarian stimulation for 20 cycles, including the administration of a GnRH antagonist (Cetrorelix, 0.25 mg daily) during the late follicular phase. There was no statistically significant difference between the groups for mean age, duration of infertility, baseline FSH concentration, cancellation rate, number of ampoules of gonadotrophin used, number of mature oocytes retrieved, oestradiol concentrations on the day of injection of human chorionic gonadotrophin (HCG), fertilization rate and number of embryos transferred. The clinical pregnancy and implantation rates in group II appeared higher than in group I, but were not significantly different (20 and 13.33% compared with 6.25 and 3.44% respectively). The addition of GnRH antagonists to ovarian stimulation protocols might be a new hope for poor responder IVF patients, but this report is preliminary and further controlled randomized prospective studies with larger sample sizes are required.     

Human menopausal gonadotrophin increases pregnancy rate in comparison with clomiphene citrate during replacement cycles of frozen/thawed pronucleate ova

In a prospective randomized study, the effect of two ovulationinduction regimens on implantation rate of frozen/thawed pronucleateova was investigated. Patients received either human menopausalgonadotrophin (HMG) or clomiphene/HMG. Ovulation induction wasdone on an individual basis using ultrasound and plasma 17-oestradiolconcentrations. Ovulation was induced with human chorionic gonadotrophin(HCG) when the leading follicle reached a diameter of 18 mm.Pronucleate ova had been frozen using the slow-freezing methodof Lassalle et al. (1985) (Fertil. Steril., 44, 645–651)and were thawed in synchrony with the age of the endometrium.Both groups of patients were comparable for age, indicationfor in-vitro fertilization, pre-ovulatory 17-oestradiol concentration,number of large follicles and number and quality of embryostransferred. The only difference found was that HCG was administered1 day earlier in the HMG group compared to the clomiphene/HMGgroup (P< 0.01). Using univariate analysis, the pregnancyrate was higher in patients stimulated with HMG alone comparedto those stimulated with clomipheneöHMG (27 versus 15%respectively; P < 0.03), when HCG was administered laterin the menstrual cycle (P < 0.01) and when more and betterquality embryos were transferred (P < 0.01). Using multivariateregression analysis, the influence of the stimulation on pregnancyrate was even more pronounced (P < 0.01) when the day ofHCG administration and the number and quality embryos transferredwere taken into account. Therefore, we conclude that HMG aloneincreases pregnancy rate compared to clomiphene/HMG during replacementcycles of frozen/thawed pronucleate ova. These data suggestthat HMG results in a better endometrium receptivity for embryos.This could be important not only for embryo replacement cyclesbut also for ovulation induction in general.     

Outcome of in-vitro fertilization through natural cycles in poor responders.

This prospective study examines the benefits of using natural cycles instead of stimulated cycles in poor responders to in-vitro fertilization (IVF) treatment. Eleven patients in whom puncture was cancelled or who failed to conceive because of a poor response were included in the analysis. The data for natural cycles (n = 16) were compared with data obtained during previous stimulated cycles (n = 25) in the same women. Out of 16 natural cycles, 13 (81.3%) were scheduled for oocyte retrieval compared to 13 out of 25 stimulated cycles (52%). Eighteen metaphase II oocytes were obtained during stimulated cycles, giving a 66% fertilization rate. In natural cycles, 11 metaphase II oocytes were available giving a fertilization rate of 78.6%. A mean number of 51.5 +/- 25 ampoules of gonadotrophins per cycle were used during ovarian stimulation. Three clinical pregnancies were obtained after embryo transfer in natural cycles (18.8%/started cycle) compared to none in stimulated cycles. Our findings demonstrate that an encouraging number of pregnancies can be achieved by IVF during natural cycles in poor responders to ovarian stimulation. This may not be the first approach to consider in IVF but it should be offered as an alternative after two ovarian response failures using classical protocols of stimulation.     

Preliminary results on transvaginal tubal embryo stage transfer (TV-TEST) without ultrasound guidance

IVF procedures have been increasingly used in male subfertility for both therapeutic and diagnostic purposes. As we assume a positive influence of the tubal milieu on the early embryonal development, any therapy should aim at intratubal embryo transfer. In this respect, only invasive techniques such as laparoscopy or laparotomy have been available hitherto (Asch et al., 1986; Balmaceda et al., 1988; Diedrich et al., 1989). Transvaginal intra-tubal embryo stage transfer (TV-TEST) was performed in 15 patients. After stimulation with clomiphene/HMG, HMG or GnRHA/HMG, patients with a follicle size of 18 mm were given 10000 IU HCG. Thirty six hours later, the transvaginal oocyte retrieval was performed without anaesthesia. Altogether, 109 oocytes were recovered. A fertilization rate of 30.3% yielded 33 embryos. Forty-eight hours after oocyte retrieval, the TV-TEST was performed without anaesthesia, in the course of which a maximum of three embryos in the 2- to 8-cell stage were transferred into one tube. Six of these patients are now pregnant.     

Endocrinology: Isolated polycystic morphology in ovum donors predicts response to ovarian stimulation

The isolated finding of polycystic-appearing ovaries on ultrasoundexamination of normal women is not uncommon. The purpose ofthis study was to determine the clinical significance of polycysticovaries in a population of healthy, non-hirsute, fertile womenpreparing to undergo ovarian stimulation. We evaluated whetherthe finding of polycystic ovaries in oocyte donors predictsa different response to ovarian stimulation when compared todonors with normal-appearing ovaries. Furthermore, we examinedwhether oocytes from polycystic ovaries had the same capacityfor fertilization and development as those retrieved from normalovaries. In all, 11 donors with polycysticappearing ovarieswere compared prospectively to 13 donors with normal-appearingovaries who were undergoing ovarian stimulation during the sametime interval. The two groups were similar in age and baselineandrogen concentrations. Significantly more oocytes were producedby the polycystic group for the amount of human menopausal gonadotrophin(HMG) administered (P < 0.05). In addition, all previouscycles completed by these 24 donors were compared (polycysticgroup: total of 31 cycles; normal group: total of 37 cycles).The donors with polycystic ovaries required less HMG to obtainoptimal stimulation (P < 0.05), attained a greater peak oestradiolconcentration (P < 0.05), produced a greater number of follicles(P < 0.05) and oocytes (P < 0.01) and a higher percentageof mature oocytes (P < 0.05). Furthermore, they achieveda higher peak oestradiol/HMG (P < 0.01) and oocytes/HMG ratio(P < 0.01). Also, the oocytes from donors with polycystic-appearingovaries, in contrast to reports of oocytes from women with polycysticovary syndrome, demonstrated superior maturity (P < 0.05)and similar fertilization, clinical pregnancy and miscarriagerates as oocytes from normal-appearing ovaries. In conclusion,visualizing polycystic ovaries in normal women predicts a heightenedsensitivity to HMG. Nonetheless, women with polycystic-appearingovaries are excellent oocyte donors, producing significantlymore oocytes than donors with normal-appearing ovaries. Furthermore,the oocytes collected are of normal quality and have the samecapacity for fertilization and embryo development.     

Timed oocyte collection in an assisted conception programme using GnRH analogue

Three-hundred-and-twenty-five patients on an assisted conception programme underwent 378 cycles of oocyte retrieval (OPU) following ovarian stimulation using a GnRH analogue and human menopausal gonadotrophins (HMG), a regimen which allows programmed cycles and delayed oocyte retrieval. Eighteen cycles were excluded (failed OPU in three and failure of fertilization in 15). In 360 cycles, patients completed their treatment with either in-vitro fertilization/embryo transfer (IVF/ET) (116) or gamete intra-Fallopian transfer (GIFT) (244), of which 241 took place at the normal time and 119 were delayed for 24 h or more to avoid weekend operating. The overall pregnancy rate per OPU was 29.5%, with the IVF group being 24.1% and the GIFT group being 32.8%. In the group of patients in whom OPU was delayed, the pregnancy rate was significantly higher in each sub-group than in the corresponding non-delayed sub-group (overall, 37.0 versus 25.7%; IVF/ET, 38.5 versus 16.9%; GIFT, 36.3 versus 31.1%). There was a significantly higher number of oocytes collected, gametes/embryos transferred in the group whose OPU had been delayed. In patients receiving GnRH analogue and HMG for ovarian stimulation, delaying oocyte retrieval is not harmful, may result in an improved outcome and allows OPU to be performed on routine operating lists. This facility, together with the improved pregnancy rates associated with this protocol of ovarian stimulation should improve the cost-effectiveness of assisted conception programmes.     

Experience with zona drilling and zona cutting to improve fertilization rates of human oocytes in vitro

Zona drilling (ZD) and zona cutting (ZC) were used in an IVF programme to assist fertilization in semen defect patients. Twenty-seven patients consented to ZD where acidified Tyrode's was used to create a hole in the zona pellucida. In 19 patients, ZD increased the fertilization rate to 29% compared with 8% (P less than 0.001) in their routine IVF cycles, and in eight patients precluded from routine IVF, a fertilization rate of 14% was achieved. Twenty-two patients consented to ZC where a slit in the zona is made mechanically. In 12 patients ZC increased the fertilization rate to 31% compared with 14% (P less than 0.01) from previous routine IVF cycles, and in 10 patients precluded from routine IVF, a fertilization rate of 34% was achieved. In 13 cycles, 68 uncut control oocytes were inseminated. In five cycles both control and ZC oocytes were fertilized (n.s.d.). In eight cycles no control oocytes were fertilized compared with 27% of ZC oocytes. The polyspermy rate was 4.6%. Twenty-four per cent of ZD and 12% of ZC (P less than 0.01) oocytes and embryos were degenerate after 42 h. Both ZD and ZC can increase the fertilization rate of sub-optimal semen, however, in our hands neither technique produced a pregnancy.